Intermediate filaments (IF) along with microtubules (MT) constitute the chief cytoskeletal elements in both invertebrate and vertebrate neurons. Alterations in neuronal IF ultrastructure and distribution are associated with a variety of brain disorders, including Alzheimer's disease. The proposed research is designed: (1) to identify the polypeptides which comprise IF in mammalian as well as in invertebrate neurons; (2) to characterize the physical-chemical mechanism of neural IF assembly; (3) to investigate the effects of biologically relevant parameters on the assembly and organization of neural IF; (4) to investigate similarities and differences in the composition of different types of neural IF and of their constitutent polypeptides; (5) to investigate the possibility that neural IF and MT may interact via associations mediated by specific polypeptides, and (6) to determine the biochemical basis for structural alterations of neural IF in Alzheimer's disease. The data obtained from this research should therefore shed light upon the biochemical mechanisms underlying the assembly, structural organization, and functions of IF in normal as well as in diseased neurons.